AJP - Heart and Circulatory Physiology, Vol 244, Issue 2 281-H288, Copyright © 1983 by American Physiological Society
Tricarboxylic acid cycle metabolites during ischemia in isolated perfused rat heart
K. J. Peuhkurinen, T. E. Takala, E. M. Nuutinen and I. E. Hassinen
Isolated rat hearts were, after a retrograde perfusion by the Langendorff
procedure, rendered ischemic by lowering the aortic pressure to zero. The
rate of proteolysis and temporal patterns of the changes in the
concentrations of the metabolites of the tricarboxylic acid cycle, related
amino acids, ammonia, and breakdown products of the adenine nucleotides
were determined. The most significant change in the amino acid metabolism
was a decrease of the proteolysis to one-tenth and a large accumulation of
alanine, which was almost stoichiometric to the degradation of aspartate
plus asparagine. The accumulation of malate and succinate was small
compared with the metabolic net fluxes of aspartate and alanine. The
metabolic balance sheet suggests that aspartate was converted to alanine. A
prerequisite for this would be a feed in of carbon of aspartate to the
tricarboxylic acid cycle as oxalacetate, reversal of the malate
dehydrogenase, and production of pyruvate by the malic enzyme reaction.
Alanine accumulating during ischemia is not glycolytic in origin but occurs
through a concerted operation of anaplerotic reactions and tricarboxylic
acid cycle metabolite disposal. The data also suggest that the potentially
energy-yielding reduction of fumarate to succinate is not significant in
the ischemic myocardium.
